Most commercial assays for intact parathyroid hormone (iPTH) cross-react with non-PTH1-84 fragments (likely to be PTH7-84). We aimed to evaluate a whole PTH assay that measured only PTH1-84 by comparing it with an assay measuring iPTH levels during parathyroidectomy in secondary hyperparathyroidism (HPT). Twenty-eight patients with secondary HPT who underwent total parathyroidectomy with autotransplantation served as subjects. Blood samples for postoperative assay were drawn after anesthesia; immediately prior to excision of the last parathyroid gland; and at 5, 10, and 15 minutes after excision. The PTH7-84 level was calculated by subtracting the whole PTH value from the iPTH value. Plasma whole PTH decreased more rapidly than iPTH after parathyroidectomy (p < 0.0001). PTH levels that decreased by 50% or more from levels prior to excision to 10 minutes after excision were used to predict successful parathyroidectomy; decreases in whole PTH substantiated curative surgery for all patients without introducing false-positive and false-negative results. iPTH levels decreased by at least 50% in only 16 patients at 10 minutes after excision without false-positive results. Out of 11 cases in which iPTH decreased less than 50%, two were true-negatives and nine were false-negatives. Decreases in whole PTH levels more accurately reflect surgical outcome than do decreases in iPTH levels during parathyroidectomy in secondary HPT patients. Even though the quick iPTH assay is used infrequently during surgery for secondary HPT, our results suggest that a quick whole PTH assay may be more useful than the iPTH assay currently used in parathyroidectomy procedures for secondary HPT.

OBJECTIVE

The aim of this study was to identify the predictors of early postoperative hypocalcemia after a total/near total thyroidectomy in order to select patients for prompt treatment to prevent symptomatic hypocalcemia.

METHODS

Patients with hypocalcemia within 24 h of surgery were identified as Group I and normocalcemic patients as Group II. The perioperative serum total calcium (tCa, ionized calcium (iCa) and intact parathormone (iPTH) were measured perioperatively. Skin closure (SC) was accepted as the reference time point. Data are expressed as the mean +/- SEM.

RESULTS

The study included 73 patients. Hypocalcemia (Group I) was detected in 40 patients (54%) within the first 24 h postoperatively. Symptomatic hypocalcemia was detected in 40% of the patients in Group I. Intact parathormone values at 10 min of SC were significantly lower in Group I (P = 0.001). IPTH measurement at 10 min of SC showing a>>/=30% decrease had a 92.3% sensitivity and 92.6% specificity in predicting hypocalcemia after a total/near total thyroidectomy. The postoperative day 15 mean tCa, iCa, and iPTH values were similar in both groups of patients. The mean iPTH level was 16.79 +/- 2.5 pg/dl at 10 min after SC in patients who developed symptomatic hypocalcemia.

CONCLUSIONS

Intact parathormone measurement 10 min after SC is helpful to predict early postoperative hypocalcemia. An IPTH decrease>>/=30% at this time point estimates the risk of postoperative hypocalcemia.

The role of the kidney, liver, and bone and/or muscle, in the metabolic clearance of parathyroid hormone (PTH), has been examined in man. Serum was obtained from the femoral artery and the renal, hepatic, and femoral veins of nine hyperparathyroid patients undergoing selective venous catheterization. The concentration of immunoreactive parathyroid hormone (IPTH) was measured in the samples by radioimmunoassay using an antiserum predominantly specific for the aminoterminal (N-terminal) portion of the PTH molecule. Gel filtration of hyperparathyroid sera demonstrated this antiserum to measure essentially only intact PTH. The mean arteriovenous (AV) difference measured across the liver was 44%; across the kidney, 34%; and across the leg, 16%. These arteriovenous differences were all statistically significant (p less than 0.005). A significant positive correlation was found between the AV difference in IPTH across the kidney and the serum calcium concentration (r = 0.50, p less than 0.05). These studies suggest that both the liver and the kidney play major roles in the clearance of PTH in man and indicate that PTH is cleared by bone and/or muscle as well. The correlation observed between the serum calcium concentrations and the AV differences in IPTH across the kidney suggest that the rate of clearance of PTH in man may be modulated by changes in the concentration of serum calcium.

Intravenous aminohydroxypropylidene bisphosphonate (APD) normalizes serum calcium in most hypercalcemic cancer patients, however the optimal therapeutic scheme has not been established. We compared in a randomized prospective trial the efficacy and the tolerance of APD given as a 3-day treatment of daily 2-h infusions of 0.5 mg/k.d in 250 ml of saline (group A) with single 24-h infusions of 1.5 mg/kg (group B) or of 0.5 mg/kg in 1 liter of saline (group C). Thirty-three cancer patients remaining hypercalcemic after a 48-h rehydration period were included and monitored daily until normocalcemia or treatment failure was documented. Serum calcium became normal in all but 1 patient (in group C) but remained normal for only 1 or 2 days in 4 other patients (1 in A, 1 in B, 2 in C). The decline in total or ionized serum calcium was slightly less marked in group C than in the two other groups, but the differences were not significant. The fall of fasting urinary calcium excretion was however significantly less rapid in group C (p less than 0.05 from day 1 to day 4). Serum concentrations of iPTH and 1,25-dihydroxyvitamin D [1,25-(OH)2D] increased significantly in the three groups. Serum magnesium concentrations fell slightly from 1.41 +/- 0.05 to 1.28 +/- 0.04 mEq/liter (p less than 0.001) after rehydration but returned to normal after APD administration (day 5, 1.52 +/- 0.04 mEq/liter, p less than 0.001 versus day 0).(ABSTRACT TRUNCATED AT 250 WORDS)

Children suffering severe burns develop progressive vitamin D deficiency because of inability of burned skin to produce normal quantities of vitamin D(3) and lack of vitamin D supplementation on discharge. Our study was designed to determine whether a daily supplement of a standard multivitamin tablet containing vitamin D(2) 400 IU (10 microg) for 6 months would raise serum levels of 25-hydroxyvitamin D [25(OH)D] to normal. We recruited eight burned children, ages 5-18, whose families were deemed reliable by the research staff. These children were given a daily multivitamin tablet in the hospital for 3 months in the presence of a member of the research staff and then given the remainder at home. At 6 months, the subjects returned for measurements of serum levels of 25(OH)D,1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone (iPTH), Ca, P, albumin, and total protein as well as bone mass by dual energy X-ray absorptiometry. Serum 25(OH)D levels were compared to a group of seven age-matched burned children studied at an earlier date without the vitamin supplement but with the same method of determination of 25(OH)D at 6 months post-burn. In addition, the chewable vitamins were analyzed for vitamin D(2) content by high performance liquid chromatography. Serum concentration of 25(OH)D was 21 +/- 11(SD) ng/ml (sufficient range 30-100) with only one of the eight children having a value in the sufficient range. In comparison, the unsupplemented burn patients had mean serum 25(OH)D level of 16 +/- 7, P = 0.33 versus supplemented. Serum levels of 1,25(OH)(2)D, iPTH, Ca, P, albumin, and total protein were all normal in the supplemented group. Vitamin D(2) content of the chewable tablets after being saponified and extracted was 460 +/- 20 IU. Bone mineral content of the total body and lumbar spine, as well as lumbar spine bone density, failed to increase as expected in the supplemented group. No correlations were found between serum 25(OH)D levels and age, length of stay, percent body surface area burn or third-degree burn. Supplementation of burned children with a standard multivitamin tablet stated to contain 400 IU of vitamin D(2) failed to correct the vitamin D insufficiency.

Treatment of secondary hyperparathyroidism and the osteodystrophy of predialysis chronic renal failure (CRF) with 1,25(OH)2D3 has been advocated by several authors, but also opposed by others for alleged renal toxicity. However, current concepts of the pathogenesis of the early occurrence of secondary hyperparathyroidism in predialysis CRF point to deficiency of 1,25(OH)2D3 as a primary factor. The aim of this study was to evaluate if administration of 1,25(OH)2D3 (0.25 microgram daily) in a dose which would not induce hypercalcemia, would improve humoral and bone histomorphometric parameters in predialysis CRF. 15 patients with predialysis CRF (mean age 51.2 +/- 16.9 years, range 13-73 years), serum creatinine 4.93 +/- 1.7 mg/dl, were treated with the vitamin D metabolite for an average of 16.2 +/- 11.3 months, at the end of which a transiliac bone biopsy for histomorphometry was performed. In addition, 23 patients comparable for age, serum creatinine and causes of renal failure, served as controls. Treatment did not induce hypercalcemia nor adversely modify the rate of decline of renal function. Alkaline phosphatase fell significantly while immunoreactive parathyroid hormone (iPTH) and osteocalcin showed a moderate, not significant, decrease. Compared to the control patients, the bone histomorphometric parameters active resorption surface and active osteoblastic surface were significantly lower and almost normalized by treatment. In conclusion, the study provides conclusive evidence of the absence of toxicity of the metabolite at the low doses employed, together with good therapeutic response on bone histology. Treatment at this dosage could be made in the early stages of predialysis CRF without need of close and continuous monitoring of serum biochemical parameters.

Comparing patients with primary hyperparathyroidism (PHP) to a normocalcemic control population, those with PHP have a higher incidence of cardiovascular disease and cardiac abnormalities. This study aimed at correlating cardiac findings (valvular and myocardial calcification, myocardial hypertrophy) with clinical data (age, sex, clinical manifestation, nephrolithiasis, nephrocalcinosis, hypertension, skeletal abnormalities, hypercalcemic syndrome) and biochemical data (serum calcium, serum phosphate, serum iPTH level, serum creatinine). A group of 132 consecutive patients with surgically verified PHP (94 women, 38 men; ages 15-86, mean age 57 +/- 16 years) were included in this study. Blood chemistry, clinical presentation, radiography, and echocardiography were carried out in all patients for univariate and multivariate analyses of all parameters. There was no statistical correlation between clinical symptoms, biochemical data, and cardiac calcific alterations. Typical skeletal manifestations (osteolysis/subperiostal resorption) and valvular calcifications were significantly correlated to left ventricular hypertrophy (p = 0.005). Cardiac abnormalities such as calcific myocardial deposits or mitral and aortic valvular calcifications do not correlate with laboratory findings and clinical presentation at the time of diagnosis. There was no biochemical or clinical variable that could predict the frequency or severity of valvular sclerosis or calcific deposits in the myocardium. However, PHP-related skeletal abnormalities and valvular calcification were predicting factors for left ventricular hypertrophy, a reversible cardiac manifestation of PHP. Myocardial hypertrophy is more often found with classic symptomatic PHP with osseous abnormalities.

Serum bone GLA protein (BGP) was measured by radioimmunoassay in 42 patients (age, 47.5 +/- 16.6 years; serum creatinine, 4.32 +/- 1.9 mg/dl) with predialysis chronic renal failure (CRF). Nineteen patients were studied within a short period of time, while 23 were followed with repeated measurements of serum BGP, creatinine, iPTH, and alkaline phosphatase (AP) for a mean period of 17.1 +/- 8.1 months. Eleven of these patients were treated with 1,25(OH)2D3 for a mean of 16.8 +/- 6.4 months. In 23 patients at various stages of CRF, a transiliac bone biopsy was performed for histomorphometric evaluation. In the untreated patients, serum BGP was higher than normal and showed a positive correlation with creatinine levels (P less than 0.001). Serum BGP was also positively correlated with iPTH, AP, serum phosphate, active resorption surface, active osteoblastic surface, osteoid surface, and volume. During treatment with 1,25(OH)2D3, BGP, iPTH, and AP were significantly lower than in the untreated patients. The reduction in iPTH and BGP was proportional, while BGP and AP no longer correlated. Repeated measurements of BGP during the long-term follow-up showed a progressive rise in the untreated patients and a downward course of BGP levels during treatment. In conclusion, serum BGP increases progressively in CRF, rising with advancing renal damage in close correlation with iPTH, AP, and the severity of renal osteodystrophy. Treatment with 1,25(OH)2D3 causes a parallel decline in BGP and iPTH levels and dissociation between BGP and AP can be observed. Compared to AP, BGP seems to be a more reliable index of secondary hyperparathyroidism and potentially more useful in the long-term monitoring of treatment with 1,25(OH)2D3.

Of 100 consecutive patients with recurrent renal calculi, 43 had idiopathic hypercalciuria (IH) on outpatient evaluation. Hypercalciuria was classified as diet-dependent or fasting; all patients had normal serum iPTH and urinary cyclic AMP, and serum phosphate and TmPO4/GFR were reduced in IH compared to normocalciuric stone formers. In 16 patients with IH, clearance studies revealed an elevated urine flow are factored for GFR (V/GFR) as compared with normal controls (p less than 0.05). In 12 patients, serum PTH was normally suppressed by calcium infusion but TmPO4/GFR was persistently reduced. Acute and chronic phosphate administration significantly reduced urine calcium excretion but did not correct the abnormal V/GFR. We conclude that in IH of both the fasting and the diet-dependent type, there is a defect in the proximal tubular reabsorption of sodium and fluid as well as PTH-independent tubular phosphate wasting. The proximal tubular defect is not a consequence of hypercalciuria nor of phosphate depletion but may be a cause of these abnormalities.

BACKGROUND

Quick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay.

METHODS

This study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value.

RESULTS

The percentage of 7-84 PTH in iPTH in plasma samples was 27.5 +/- 14.4% in pHPT and 39.6 +/- 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 +/- 10.8 and 32.0 +/- 11.3% of the preexcision level at 5 minutes, 10.6 +/- 7.7 and 21.1 +/- 8.8% at 10 minutes, and 8.5 +/- 4.9 and 16.1 +/- 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 +/- 20.2 and 66.1 +/- 19.7% at 5 minutes, 28.6 +/- 16.6 and 53.6 +/- 18.1% at 10 minutes, and 14.2 +/- 9.0 and 41.0 +/- 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 +/- 85.9 and 62.1 +/- 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands.

CONCLUSIONS

The percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.

OBJECTIVE

It was discovered that an immunoreactive large carboxy-terminal parathyroid hormone (PTH) fragment (large C-PTH), likely 7-84 PTH, is present in the circulation. However, very little is known about the production and metabolism of this large C-PTH. Combining a whole molecule PTH (whole PTH) immunoradiometric assay (IRMA) specifically for 1-84 PTH and an intact PTH (iPTH) IRMA for the sum of 1-84 PTH and large C-PTH, we were able to assess the circulating level of this large C-PTH as well as the glandular secretion and metabolism of this large C-PTH in primary hyperparathyroidism (pHPT).

METHODS

This study consisted of two patient groups consisting of 77 pHPT patients with a single adenoma. Of these, 43 comprised the venous sampling study group and 70 comprised the intra-operative PTH study group. (Seven patients belonged only to the former group, 34 patients to only the latter group, and 36 patients to both groups.) Preoperatively, blood samples were drawn from the bilateral internal jugular vein by ultrasonographic guidance and from the peripheral vein (n=43). During surgery, blood samples were drawn after anesthesia (basal level), before excision (pre-excision level) of one enlarged parathyroid gland, and at 5, 10, and 15 min post-excision (n=70).

RESULTS

There were 26 patients whose iPTH assay levels differed by more than 10% between the right and left internal jugular. In 24 of the 26 patients, the large C-PTH levels obtained from the adenoma side were significantly higher than those from the contralateral side (117+/-135 vs 43+/-33 pg/ml, P<0.001). The plasma whole PTH values decreased more rapidly than the iPTH values after parathyroidectomy (P<0.001).

CONCLUSIONS

Our study has demonstrated that the large C-PTH, likely 7-84 PTH, is directly released from the parathyroid gland in humans. Since the half-life of 1-84 PTH is much shorter than large C-PTH, likely 7-84 PTH, it would be advantageous to use an assay that specifically measures 1-84 PTH for intra-operative monitoring of parathyroidectomy.

OBJECTIVE

To prospectively assess the effectiveness of total parathyroidectomy and autotransplantation using a subcutaneous injection technique to treat secondary hyperparathyroidism.

METHODS

We used this method to treat 14 patients with secondary hyperparathyroidism. The short-term outcome, up to 16 months after surgery, was monitored by measuring calcium, inorganic phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase levels. We considered a graft viable when the ratio of iPHT in antecubital venous blood from the grafted arm to that from the nongrafted arm exceeded 1.5.

RESULTS

Autografted parathyroid tissue was functional in 12 (85.7%) patients. An iPTH ratio>> or =1.5 in the grafted arm relative to the nongrafted arm was observed from 2 weeks after surgery, peaking at 1 month. The grafted tissue continued to be biochemically functional 16 months after surgery in 12 patients.

CONCLUSIONS

These findings suggest that total parathyroidectomy and forearm autotransplantation using the subcutaneous injection technique is a possible alternative to Wells' method for surgical treatment of secondary hyperparathyroidism.

Peripheral bone density measurements are scarce and the factors, which predict bone mineral density at these sites, especially in children, are not clearly known. In this study, age, height, weight and alkaline phosphatase had a significant association on peripheral bone mineral density in healthy Indian school girls.

BACKGROUND

Factors that lead to the attainment of peak bone mass at peripheral sites, during period of growth are not clearly known.

METHODS

Six-hundred and sixty-four randomly selected 7- to 17-year-old girls from upper and lower socioeconomic status (USES/LSES) schools were assessed clinically and a recording of their height and weight was undertaken. Serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) were measured in all of them. Bone mineral density (BMD) was measured at the distal forearm (BMDdf) and calcaneum (BMDca) by peripheral dual energy X-ray absorptiometry (pDXA).

RESULTS

Girls belonging to the USES were significantly taller (149.7 +/- 12.3 cm vs 144.4 +/- 11.9 cm; P < 0.001) and weighed more (44.3 +/- 12.9 kg vs 35.9 +/- 10.0 kg; P < 0.001) than girls from the LSES. USES girls had a significantly higher mean serum calcium (9.3 +/- 0.7 mg/dl vs 9.2 +/- 0.8 mg/dl; P < 0.05) and significantly lower alkaline phosphatase (316 +/- 166 IU/l vs 423 +/- 228 IU/l; P < 0.01) and iPTH (29.9 +/- 18.4 pg/ml vs 45.7 +/- 64.6 pg/ml; P < 0.01). There was no significant difference in mean serum phosphorus and 25-OHD levels between the two groups. USES subjects had higher BMD at both sites than LSES subjects. BMDdf and BMDca increased with age and tended to plateau by 16 years and 12 years of age respectively in both the groups. Age, height and weight explained approximately 50% of the variability, while biochemical parameters explained approximately 30% of variability in BMD at both the sites. The only biochemical parameter which had a significant association with BMD was ALP at the distal forearm.

CONCLUSIONS

In conclusion, age, nutrition, height and weight are significantly associated with BMD at peripheral sites.

Bone mineral status has extensively been investigated in adult thalassemics but less in thalassemic children. This study involves measurements of the bone mineral density (BMD), various demographic and biochemical parameters in 47 thalassemic children and 50 healthy controls with comparable age, sex, socioeconomic and regional distribution. Patients have significantly higher aspartate aminotransferase, alanine aminotransferase, phosphorous, osteocalcin, serum carboxy terminal teleopeptide fragment of type I collagen, intact parathyroid hormone (iPTH) and ferritin levels while they have significantly lower 25-hydroxy vitamin D (25OH-D), alkaline phosphatase and z-scores both at lumbar and femur compared to controls. Patients with high iPTH (30%) had significantly lower z-scores and 25OH-D while larger osteocalcin. We conclude that a significantly lower BMD in beta-thalassemic children compared with their healthy counterparts is a complex process and may partially attributed to their slower physical development, caused by iron overload and chelation therapy which may influence the liver as well as the endocrine tissues.

Preferential expansion of the plasma volume by infusion of salt-poor hyperoncotic albumin solution decreases sodium reabsorption by the proximal tubule. The present micropuncture studies test the thesis that albumin infusion depresses proximal reabsorption by an effect unrelated to expansion of the plasma volume, perhaps due to an effect of parathyroid hormone (PTH) on proximal sodium reabsorption. Infusion of salt-poor hyperoncotic albumin significantly decreased plasma ionized calcium, increased immunoreactive PTH (iPTH) in plasma, decreased sodium reabsorption by the proximal tubule, and increased phosphate clearance. In contrast, infusions of albumin, in which the ionized calcium was restored to normal plasma levels, had no significant effect on ionized calcium, iPTH, proximal reabsorption, or phosphate clearance in intact dogs. Similarly, in parathyroidectomized animals given a constant replacement infusion of PTH, albumin infusion had no significant effect on proximal reabsorption or phosphate clearance. Plasma volume was markedly expanded following albumin infusion in all groups of dogs. These findings (a) indicate that PTH plays a significant role in the decrease in sodium reabsorption by the renal proximal tubule after salt-poor hyperoncotic albumin infusion, and (b) dissociate preferential expansion of the plasma volume from decreases in sodium reabsorption by the proximal tubule.

25-Hydroxyvitamin D (25OHD) may influence bone turnover. We compared the dynamics of bone markers in 30 infants on vitamin D supplementation (≅550 IU/day) with different degrees of hypovitaminosis D (25OHD <11 ng/ml - deficiency vs. ≥ 11 <20 ng/ml - insufficiency). Baseline and follow-up (after 10 weeks), 25OHD, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), alkaline phosphatase (ALP), PTH, osteocalcin (OC), N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX), and amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) were measured. None of the newborns had craniotabes, hypocalcemia or hyperparathyroidism. The median (Q1;Q3) 25OHD increased from a baseline of 8.45 (7;11.9) ng/ml to 54.6 (34.7;67.3) ng/ml (p<0.001). The baseline 25OHD negatively correlated with total increment of 25OHD (r=-0.54; p=0.002). There were changes in ALP (241 vs. 331 IU; p<0.001), 1,25(OH)(2)D (48 vs. 95.5 pg/ml, p<0.001), OC (88.8 vs. 159.1 ng/ml, p<0.001), PINP (3886 vs. 2409 ng/ml; p<0.001), CTX (1.6 vs. 1.1 ng/ml; p<0.001), and NT-proCNP (75.1 vs. 35.1 pmol/l; p<0.001). Vitamin D deficient infants at baseline, compared to the insufficient group, revealed significantly higher percentage changes for 25OHD (745% vs. 167%, p<0.0001), OC (113% vs. 40%, p<0.05) and 1,25(OH)(2)D (95% vs. 58%, p<0.05).

CONCLUSIONS

Vitamin D supplements had little to no impact on markers of bone turnover in term infants in the first few months of life, with the exception of osteocalcin. Ten weeks of cholecalciferol supplementation at a dose of 550 IU/day led to a marked increase of 25OHD concentration. The magnitude of 25OHD increment was inversely related to vitamin D status at baseline. Irrespective of the severity of vitamin D deficiency, a secondary hyperparathyroidism with elevated iPTH, ALP, phosphaturia or hypophosphatemia was not observed in the studied neonates.

Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid fe of hyperthyroidism. The prevalence of hypercalcaemia was 51.1% using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9% of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa%) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serarathyroid function.

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.

Circulating levels of parathyroid hormone (PTH) rise with age in normal men and women. To resolve the basis for this observation we measured iPTH in 137 normal men and women, age 23 to 85 years, using two antisera which responded to different portions of the PTH molecule. A midmolecule assay (Mid-PTH) employed antiserum NG-5, which recognizes mid- and carboxy-terminal portions of hPTH, whereas antiserum CK-67, which recognizes determinants in the 1-34 hPTH sequence, was used to measure intact PTH (NH2-PTH). Two-hour fasting urine was collected for measurement of creatinine clearance and excretion indices of phosphorus and cyclic AMP. Serum was analyzed for 25-hydroxyvitamin D (25-OHD) in addition to iPTH. Mid-PTH rose significantly with age in the 72 women (r = 0.38, p less than 0.001) and in the 65 men (r = 0.40, p less than 0.001). NH2-PTH rose with age in women (r = 0.23, p less than 0.05), but a change in men was not significant (r = 0.19, n.s.). Cyclic AMP excretion rose significantly with age in both women (r = 0.42) and men (r = 0.41), whereas phosphorus excretion rose significantly in women only (r = 0.32, p less than 0.01). 25-OHD levels were 27.5 +/- 1.3 ng/ml for women and 26.1 +/- 1.2 ng/ml for men. No change in 25-OHD was observed with age in women, and a significant decrease in men was due entirely to extremely high values in three young subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte sodium-potassium (Na+/K+)-ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6-16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean +/- SEM 2,156 +/- 110 micromol P/l erythrocyte per hour vs. 3,165 +/- 175, P < 0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90 +/- 0.07 mmol/mmol versus 0.51 +/- 0.06 respectively, P < 0.01. The corresponding iPTH levels were 5.9 +/- 0.6 pmol/l and 5.1 +/- 0.7, P < 0.05. The Na+/K+-ATPase activity increased significantly (2,769 +/- 169 micromol P/l erythrocyte per hour vs. 2,156 +/- 110 in the control period, P < 0.01) and the Na+/Li+ countertransport decreased (268 +/- 28 micromol Li/l erythrocyte per hour vs. 328+26 in the control period, P < 0.03). The bone mineral density Z score rose from -1.3 +/- 0.26 to -0.8 +/- 0.22 (P < 0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.

The effects of 40 mg of prednisone given daily for 5 days to normal individuals on serum levels of bone Gla-protein (BGP), alkaline phosphatase, calcium phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone (S-iPTH) and on renal excretions of calcium, phosphate and hydroxyproline were evaluated in a double-blind, placebo controlled study. In the prednisone group a 75% decrease (P less than 0.001) was found in serum BGP compared to a 6% decrease (P less than 0.05) in serum alkaline phosphatase. The renal hydroxyproline excretion remained unchanged. Serum calcium was unchanged while the fasting urinary calcium excretion showed a 2-fold increase (P less than 0.001). Serum 1,25-dihydroxyvitamin D increased (P less than 0.01) in spite of unchanged serum 25-hydroxyvitamin D, serum phosphate and parathyroid function (as judged by S-iPTH and the maximal tubular reabsorption capacity for phosphate (TmP/GFR]. The data suggest a direct inhibition of osteoblast number and/or function by short-term glucocorticoid administration with unchanged bone resorption leading to a negative bone mineral balance. The increase in serum 1,25-dihydroxyvitamin D is probably due to a direct stimulation by glucocorticoids of the renal 1 alpha-hydroxylase. The effects of the vitamin D metabolite, however seem to be blunted.

Acute PTH administration enhances final urine acidification in the rat. HCl was infused during 3 h in rats to determine the parathyroid and renal responses to acute metabolic acidosis. Serum immunoreactive PTH (iPTH) concentration significantly increased and nephrogenous adenosine 3H,5H-cyclic monophosphate tended to increase during HCl loading in intact and adrenalectomized (ADX) rats despite significant increments in plasma ionized calcium. Strong linear relationships existed between serum iPTH concentration and arterial bicarbonate or proton concentration (P less than 0.0001). Serum iPth concentration and NcAMP remained stable in intact time-control rats and decreased in CaCl2-infused, nonacidotic animals. Urinary acidification was markedly reduced in parathyroidectomized (PTX) as compared with intact rats during both basal and acidosis states; human PTH-(1-34) infusion in PTX rats restored in a dose-dependent manner the ability of the kidney to acidify the urine and excrete net acid. Acidosis-induced increase in urinary net acid excretion was observed in intact, PTX, and ADX, but not in ADX-thyroparathyroidectomized rats. We conclude that (a) acute metabolic acidosis enhances circulating PTH activity, and (b) PTH markedly contributes to the renal response against acute metabolic acidosis by enhancing urinary acidification.

BACKGROUND

Post-thyroidectomy hypocalcemia is among the most common complications of total thyroidectomy. The purpose of this study was to evaluate early predictive factors and long-term changes in intact parathyroid hormone (iPTH) levels in patients with transient and permanent hypocalcemia after total thyroidectomy.

METHODS

A total of 349 consecutive patients who underwent total thyroidectomy with or without neck dissection between 2009 and 2011 were reviewed. PTH, total calcium (Ca), and ionized Ca (iCa) levels were evaluated at 1 hour, and 1, 3, 5, and 7 days, and 1, 3, 6, and 12 months postoperatively. Biochemical profiles at 1 hour after total thyroidectomy in patients with transient and permanent hypocalcemia were compared. Patients with postoperative hypocalcemia were followed for 12 months.

RESULTS

Lesser preoperative serum levels of Ca and more extensive surgery were significantly associated with postoperative hypocalcemia (P < .05). The absolute level and relative decline (%) in iPTH at 1 hour were the most reliable predictors of postoperative hypocalcemia according to the receiver operating characteristics curve, with a threshold of 10.42 pg/mL and 70%. Sensitivity and specificity of the predictors were 83.4% (95% CI, 76.4-89.1), 100% (95% CI, 84.6-100.0), 84.1 (95% CI, 77.2-89.7), and 95.5% (95% CI, 77.2-99.9), respectively. Parathyroid function recovered in the first month after total thyroidectomy in 78 of 99 patients (79%) with transient hypocalcemia. However, 46 of 61 patients (74%) with a subnormal iPTH level at 3 months after surgery had permanent hypocalcemia.

CONCLUSIONS

Mean postoperative PTH level and the mean relative decline in PTH measured 1 hour postoperatively were the most reliable predictors of postoperative or permanent hypocalcemia.

OBJECTIVE

A new protocol for postoperative calcium management was developed with the aim of achieving an increase in the proportion of patients being safely discharged on the first postoperative day. We present our experience with the first 50 patients treated under this new protocol.

METHODS

A cohort study was performed involving the first 50 patients admitted for total or completion thyroidectomy, those data were then compared with a control group. Intact PTH (iPTH) was measured at 4-h postoperatively and patients with iPTH in the normal range were discharged on the first postoperative day.

RESULTS

Mean age and sex distribution were similar in both groups. Mean lowest postoperative corrected calcium levels in the study group were 2.19 mmol/l and 2.15 mmol/l in the control group (P = 0.24). Parathyroid auto-transplantation was associated with low PTH levels (risk ratio = 0.49). Over 50% of patients (n = 27) were successfully discharged on the first postoperative day in the study group and no patient required readmission. Length of stay was significantly shorter in the study group, mean 1.64 vs. 2.20 days (P < 0.05).

CONCLUSIONS

The use of iPTH accurately predicts hypocalcaemia after total thyroidectomy and can be used to facilitate safe early discharge for patients.